3BWF

Crystal structure of the human Pim1 in complex with an osmium compound

3BWF の概要

• エントリーDOI: 10.2210/pdb3bwf/pdb
• 分子名称: Proto-oncogene serine/threonine-protein kinase Pim-1, SULFATE ION, PYRIDOCARBAZOLE CYCLOPENTADIENYL OS(CO) COMPLEX, ... (4 entities in total)
• 機能のキーワード: transferase, pim1, kinase, atp-binding, phosphorylation, alternative initiation, cytoplasm, manganese, membrane, metal-binding, nucleotide-binding, nucleus, phosphoprotein, proto-oncogene, serine/threonine-protein kinase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36310.23

構造登録者

Maksimoska, J.,Filippakopoulos, P.,Knapp, S.,Meggers, E. (登録日: 2008-01-09, 公開日: 2008-06-24, 最終更新日: 2024-02-21)

主引用文献

Maksimoska, J.,Williams, D.S.,Atilla-Gokcumen, G.E.,Smalley, K.S.,Carroll, P.J.,Webster, R.D.,Filippakopoulos, P.,Knapp, S.,Herlyn, M.,Meggers, E.
Similar biological activities of two isostructural ruthenium and osmium complexes.
Chemistry, 14:4816-4822, 2008

PubMed Abstract: In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half-sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205 Lu melanoma cells, activation of the Wnt signaling pathway, IC(50) values against the protein kinases GSK-3beta and Pim-1, and binding modes to the protein kinase Pim-1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three-dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.

PubMed: 18425743
DOI: 10.1002/chem.200800294

実験手法

X-RAY DIFFRACTION (2.35 Å)